Article
Psychiatry
Raphael Hirtz, Lars Libuda, Anke Hinney, Manuel Foecker, Judith Buehlmeier, Paul-Martin Holterhus, Alexandra Kulle, Cordula Kiewert, Johannes Hebebrand, Corinna Grasemann
Summary: The relationship between testosterone levels in adolescent boys during puberty and depression is complex and may be influenced by genetic factors and depression status.
FRONTIERS IN PSYCHIATRY
(2021)
Article
Neurosciences
Assunta Ingannato, Silvia Bagnoli, Salvatore Mazzeo, Valentina Bessi, Sabrina Mata, Monica Del Mastio, Gemma Lombardi, Camilla Ferrari, Sandro Sorbi, Benedetta Nacmias
Summary: The study found that intermediate alleles and plasma NfL levels may potentially serve as biomarkers in ALS, with higher frequency of IAs in the patient cohort, increasing NfL levels with age at onset, and differences in NfL concentration and age at onset between bulbar and spinal onset groups.
FRONTIERS IN NEUROSCIENCE
(2021)
Article
Clinical Neurology
Jordi Creus-Muncunill, Anna Guisado-Corcoll, Veronica Venturi, Lorena Pantano, Georgia Escaramis, Marta Garcia de Herreros, Maria Solaguren-Beascoa, Ana Gamez-Valero, Cristina Navarrete, Merce Masana, Franc Llorens, Daniela Diaz-Lucena, Esther Perez-Navarro, Eulalia Marti
Summary: While most research on Huntington's disease has focused on the pathogenic effects of proteins, growing evidence indicates that small RNAs produced in the putamen of HD patients can induce HD pathology in vivo. Different species of small RNAs, including sCAG and tRNA fragments, contribute to striatal dysfunction and general transcriptomic changes, highlighting the potential for therapeutic strategies based on blocking sRNA-mediated toxicity.
ACTA NEUROPATHOLOGICA
(2021)
Editorial Material
Neurosciences
Alexandra F. Putka, Hayley S. McLoughlin
Summary: In this issue, two studies provide new insights into the pathogenesis of spino-cerebellar ataxia type 1 (SCA1) by genetically assessing the mechanistic drivers of regional vulnerability and their relationships with SCA1 phenotypes.
Review
Biochemistry & Molecular Biology
Akihisa Mori, Brittany Cross, Shinichi Uchida, Jill Kerrick Walker, Robert Ristuccia
Summary: Adenosine is widely distributed in the central and peripheral nervous systems as a key neuromodulator, with implications in the pathogenesis of neurodegenerative disorders, especially in ALS. Motor neurons affected in ALS are responsive to adenosine receptor function, with accumulating evidence supporting the benefits of adenosine A(2A) receptor antagonism.
Article
Medicine, General & Internal
Kang-Yang Jih, Kuan-Lin Lai, Kon-Ping Lin, Yi-Chu Liao, Yi-Chung Lee
Summary: This study investigated the role of HTT repeat expansions in a Taiwanese cohort with ALS. The results showed that only one out of 410 ALS patients carried an HTT allele with 39 CAG repeats and none had HTT allele with 40 or more CAG repeats. The findings suggest that the HTT allele with 39 CAG repeats may be linked to ALS susceptibility.
JOURNAL OF THE CHINESE MEDICAL ASSOCIATION
(2023)
Article
Geriatrics & Gerontology
Kang-Yang Jih, Ying-Tsen Chou, Pei-Chien Tsai, Yi-Chu Liao, Yi-Chung Lee
Summary: Screening of ALS patients and healthy controls did not reveal the presence of NOTCH2NLC GGC repeat expansion in Taiwanese ALS patients. The distribution of GGC repeat sizes did not differ significantly between the two groups.
NEUROBIOLOGY OF AGING
(2021)
Article
Neurosciences
Quan Tran, Ashani Sudasinghe, Brooke Jones, Ka Xiong, Rachel E. Cohen, David S. Sharlin, Keenan T. Hartert, Geoffrey M. Goellner
Summary: The study identified FAM171B as a novel polyQ protein with consecutive glutamine residues, widely expressed in the mouse brain with specific localization in certain regions. Bioinformatic analysis suggested its robust expression in the human brain and polymorphic polyQ tract, making it a candidate gene for a yet molecularly uncharacterized neurodegenerative disease.
Article
Endocrinology & Metabolism
Janani S. Sankar, Elizabeth Hampson
Summary: The study found that AR CAG repeat length was a significant predictor of spatial visualization test scores, but did not affect mental rotation test scores; a shorter AR was associated with lower visualization scores, while T itself predicted scores on mental rotation tests.
PSYCHONEUROENDOCRINOLOGY
(2021)
Article
Clinical Neurology
Hitoshi Aizawa, Haruhisa Kato, Koji Oba, Takuya Kawahara, Yoshihiko Okubo, Tomoko Saito, Makiko Naito, Makoto Urushitani, Akira Tamaoka, Kiyotaka Nakamagoe, Kazuhiro Ishii, Takashi Kanda, Masahisa Katsuno, Naoki Atsuta, Yasushi Maeda, Makiko Nagai, Kazutoshi Nishiyama, Hiroyuki Ishiura, Tatsushi Toda, Akihiro Kawata, Koji Abe, Ichiro Yabe, Ikuko Takahashi-Iwata, Hidenao Sasaki, Hitoshi Warita, Masashi Aoki, Gen Sobue, Hidehiro Mizusawa, Yutaka Matsuyama, Tomohiro Haga, Shin Kwak
Summary: The study evaluated the efficacy and safety of Perampanel in patients with sporadic amyotrophic lateral sclerosis (SALS). It found that Perampanel was associated with a significant decline in ALSFRS-R score, especially in the 8 mg group. Serious adverse events were more frequent in the Perampanel 8 mg group compared to the placebo group.
JOURNAL OF NEUROLOGY
(2022)
Article
Neurosciences
Zhao Zhong Chong, Daniel L. Menkes, Nizar Souayah
Summary: Amyotrophic lateral sclerosis (ALS) is a rapidly progressive and fatal neurodegenerative disorder, with C9orf72 mutations and hexanucleotide repeat expansion (HRE) identified as major causes. The HRE expansion results in toxic gain-of-function and loss-of-function of C9ORF72, leading to RNA and dipeptide repeats inducing toxicity, and impairment of autophagy and nucleocytoplasmic transport, respectively. Understanding the mechanism of C9ORF72 HRE pathogenesis will aid in the identification of novel therapeutic targets for ALS.
REVIEWS IN THE NEUROSCIENCES
(2023)
Article
Clinical Neurology
Philippe Corcia, Pascal Lejeune, Patrick Vourc'h, Stephane Beltran, Anne-Sophie Piegay, Helene Blasco, Vincent Meininger
Summary: This study characterized the prototypical phenotype of patients with amyotrophic lateral sclerosis (ALS) associated with PFN1 mutations and identified clinical indications for testing mutations in this gene. The main clinical findings for familial ALS linked to PFN1 were identified as pedigrees with over five cases, an onset age around 50 years, onset in the lower limbs, and the absence of cognitive impairment. The similarities with other ALS mutations prompt a review of ALS classifications based on both phenotype and genotype.
EUROPEAN JOURNAL OF NEUROLOGY
(2023)
Article
Genetics & Heredity
Jay P. Ross, Fulya Akcimen, Calwing Liao, Dan Spiegelman, Ben Weisburd, Nicolas Dupre, Patrick A. Dion, Guy A. Rouleau, Sali M. K. Farhan
Summary: Our study attempted to replicate the association between the CA repeat in the STMN2 gene and the risk for ALS. However, we did not find any evidence supporting this association in our case-control cohort and in genomes from different populations.
NEUROLOGY-GENETICS
(2022)
Article
Geriatrics & Gerontology
Gijs H. P. Tazelaar, Paul J. Hop, Meinie Seelen, Joke J. F. A. van Vugt, Wouter van Rheenen, Lindy Kool, Kristel R. van Eijk, Marleen Gijzen, Dennis Dooijes, Matthieu Moisse, Andrea Calvo, Cristina Moglia, Maura Brunetti, Antonio Canosa, Angelica Nordin, Jesus S. Mora Pardina, John Ravits, Ammar Al-Chalabi, Adriano Chio, Russell L. McLaughlin, Orla Hardiman, Philip Van Damme, Mamede de Carvalho, Christoph Neuwirth, Markus Weber, Peter M. Andersen, Leonard H. van den Berg, Jan H. Veldink, Michael A. van Es
Summary: Amyotrophic lateral sclerosis, a heterogeneous neurodegenerative disease, involves various pathological mechanisms including genetic risk factors and defects in DNA damage repair.
NEUROBIOLOGY OF AGING
(2022)
Review
Clinical Neurology
Thomas H. Julian, Sarah Boddy, Mahjabin Islam, Julian Kurz, Katherine J. Whittaker, Tobias Moll, Calum Harvey, Sai Zhang, Michael P. Snyder, Christopher McDermott, Johnathan Cooper-Knock, Pamela J. Shaw
Summary: Mendelian randomization studies on amyotrophic lateral sclerosis show a causal link between blood lipids and the disease risk, while factors like smoking and immune function require further investigation for confirmation. The use of high methodological standards and replication across different datasets are essential for reliable results in Mendelian randomization studies.
Article
Behavioral Sciences
Giorgio Pigato, Stella Rosson, Nicola Bresolin, Tommaso Toffanin, Fabio Sambataro, Daniele Olivo, Giulia Perini, Francesco Causin, Luca Denaro, Andrea Landi, Domenico D'Avella
Summary: This study conducted a long-term follow-up on 5 patients with treatment-resistant depression (TRD) who received vagus nerve stimulation (VNS) implant. The results showed that VNS had long-lasting effectiveness in improving symptoms and functioning in patients with severe and chronic depression. The study supports VNS as a viable treatment option for TRD due to its sustained efficacy and good tolerability.
Review
Cell Biology
Barbara Tedesco, Leen Vendredy, Vincent Timmerman, Angelo Poletti
Summary: Each protein must be correctly synthesized, folded, and transported to its appropriate location. Failure in these steps can lead to protein misfolding and potential damage. Cells have well-characterized protein quality control systems, including autophagy and chaperone-assisted selective autophagy (CASA), to minimize such issues. The CASA complex, composed of HSPA, HSPB8, and BAG3 proteins, is essential for maintaining protein homeostasis and mutations in these genes can result in (cardio)myopathies and neurodegenerative diseases. This article summarizes the current understanding of the CASA complex and discusses its involvement in diseases and potential therapeutic targets.
Article
Endocrinology & Metabolism
Maria Santa Rocca, Giovanni Minervini, Cinzia Vinanzi, Alberto Bottacin, Federica Lia, Carlo Foresta, Maria Pennuto, Alberto Ferlin
Summary: This study evaluated the frequency and type of androgen receptor (AR) gene variants in a large cohort of infertile males. The study found that patients with AR gene variants had lower sperm count, higher testosterone concentration, and higher androgen sensitivity index compared to patients without variants. Two novel potentially pathogenic AR variants were identified. Based on these findings, AR sequencing is suggested as a routine genetic test in cases of idiopathic oligozoospermia with high testosterone levels.
JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM
(2023)
Article
Medicine, Research & Experimental
Marta Chierichetti, Mauro Cerretani, Alina Ciammaichella, Valeria Crippa, Paola Rusmini, Veronica Ferrari, Barbara Tedesco, Elena Casarotto, Marta Cozzi, Francesco Mina, Paola Pramaggiore, Mariarita Galbiati, Margherita Piccolella, Alberto Bresciani, Riccardo Cristofani, Angelo Poletti
Summary: The study identified three compounds that can enhance the transcription and translation of HSPB8 and reduce the aggregation propensity of a disease-associated mutant SOD1 protein. These compounds play an important role in improving cellular proteostasis and enhancing selective autophagy, and may have significant clinical implications for treating neurodegenerative diseases and other human disorders.
Article
Clinical Neurology
Mariarita Galbiati, Marco Meroni, Marina Boido, Matilde Cescon, Paola Rusmini, Valeria Crippa, Riccardo Cristofani, Margherita Piccolella, Veronica Ferrari, Barbara Tedesco, Elena Casarotto, Marta Chierichetti, Marta Cozzi, Francesco Mina, Maria Elena Cicardi, Silvia Pedretti, Nico Mitro, Anna Caretto, Patrizia Rise, Angelo Sala, Andrew P. Lieberman, Paolo Bonaldo, Maria Pennuto, Alessandro Vercelli, Angelo Poletti
Summary: Spinal and bulbar muscular atrophy (SBMA) is a neuromuscular disease characterized by motor neuron degeneration, muscle weakness, and an expansion of the CAG triplet repeat in the androgen receptor (AR) gene. In this study, the use of the antiandrogen bicalutamide and the natural disaccharide trehalose showed promising results in ameliorating SBMA pathology in a mouse model. These compounds reduced ARpolyQ toxicity, prevented autophagic flux blockage, and improved muscle morphology and function, suggesting their potential for future clinical trials in SBMA patients.
Article
Multidisciplinary Sciences
Caterina Marchioretti, Giulia Zanetti, Marco Pirazzini, Gaia Gherardi, Leonardo Nogara, Roberta Andreotti, Paolo Martini, Lorenzo Marcucci, Marta Canato, Samir R. Nath, Emanuela Zuccaro, Mathilde Chivet, Cristina Mammucari, Marco Pacifici, Anna Raffaello, Rosario Rizzuto, Andrea Mattarei, Maria A. Desbats, Leonardo Salviati, Aram Megighian, Gianni Soraru, Elena Pegoraro, Elisa Belluzzi, Assunta Pozzuoli, Carlo Biz, Pietro Ruggieri, Chiara Romualdi, Andrew P. Lieberman, Gopal J. Babu, Marco Sandri, Bert Blaauw, Manuela Basso, Maria Pennuto
Summary: Marchioretti and colleagues demonstrate that there are reversible alterations in gene expression related to muscle contraction and mitochondrial respiration in the skeletal muscle of SBMA mice and patients. These alterations are accompanied by calcium accumulation inside the mitochondria, motor dysfunction, and late changes in muscle structure. The deregulation of expression of genes involved in excitation-contraction coupling (ECC) occurs with sexual maturity and androgen increase in the serum. Surgical castration and AR silencing alleviate the early and late pathological processes, indicating an androgen-dependent nature of these alterations.
NATURE COMMUNICATIONS
(2023)
Article
Multidisciplinary Sciences
Ramachandran Prakasam, Angela Bonadiman, Roberta Andreotti, Emanuela Zuccaro, Davide Dalfovo, Caterina Marchioretti, Debasmita Tripathy, Gianluca Petris, Eric N. Anderson, Alice Migazzi, Laura Tosatto, Anna Cereseto, Elena Battaglioli, Gianni Soraru, Wooi Fang Lim, Carlo Rinaldi, Fabio Sambataro, Naemeh Pourshafie, Christopher Grunseich, Alessandro Romanel, Udai Bhan Pandey, Andrea Contestabile, Giuseppe Ronzitti, Manuela Basso, Maria Pennuto
Summary: Prakasam and colleagues demonstrate that targeting overexpressed co-activators Lsd1 and Prmt6 with artificial miRNAs can attenuate polyQ-expanded androgen receptor toxicity, ameliorating spinal-bulbar muscular atrophy phenotypes in flies and mice. This study suggests that targeting these co-regulators could be a potential therapeutic strategy for patients with SBMA, as it helps mitigate toxic gain-of-function without exacerbating loss-of-function mechanisms.
NATURE COMMUNICATIONS
(2023)
Article
Neurosciences
Mario Luciano, Gaia Sampogna, Bianca Della Rocca, Alessio Simonetti, Pasquale De Fazio, Marco Di Nicola, Giorgio Di Lorenzo, Maria Pepe, Fabio Sambataro, Maria Salvina Signorelli, Alexia Emilia Koukopoulos, Roberto Delle Chiaie, Gabriele Sani, Andrea Fiorillo
Summary: This study investigated the relationship between affective temperaments and suicidality. It found that certain affective dispositions were associated with the onset and intensity of suicidal ideation and behaviors. Therefore, evaluating affective dispositions in clinical settings can help identify individuals at risk of suicide and develop effective preventive interventions.
Review
Psychology, Clinical
Selene Mezzalira, Emanuele Pick, Arianna Palmieri
Summary: This article investigates the importance of Nachtraglichkeit/apres-coup (N/AC) in psychoanalytic psychology and suggests potential developments. The study finds that N/AC plays a crucial role in four domains: as a metapsychological construct explaining the retroactive constitution of experience, as a cornerstone for traumatic psychopathology, as a resource for the therapeutic process in clinical settings, and as a core facet of meaning-making processes involved in memory constitution.
PSYCHOANALYTIC PSYCHOLOGY
(2023)
Article
Cell Biology
Barbara Tedesco, Leen Vendredy, Elias Adriaenssens, Marta Cozzi, Bob Asselbergh, Valeria Crippa, Riccardo Cristofani, Paola Rusmini, Veronica Ferrari, Elena Casarotto, Marta Chierichetti, Francesco Mina, Paola Pramaggiore, Mariarita Galbiati, Margherita Piccolella, Jonathan Baets, Femke Baeke, Riet De Rycke, Vincent Mouly, Tommaso Laurenzi, Ivano Eberini, Anna Vihola, Bjarne Udd, Lan Weiss, Virginia Kimonis, Vincent Timmerman, Angelo Poletti
Summary: Chaperone-assisted selective autophagy (CASA) is an important pathway for the disposal of misfolded and aggregating proteins. HSPB8 is a key player in CASA, and recent studies have discovered four novel HSPB8 gene mutations associated with neuromyopathies. These mutations result in the formation of insoluble aggregates and disrupt the proteostasis response, leading to muscle cell dysfunction and impaired sarcomere organization.
Editorial Material
Biochemistry & Molecular Biology
Solaf Mohamed Elsayed, Enza Torre, Daniela Tavian, Laura Moro, Corrado Angelini, Tawhida Y. Abdel Ghaffar, Khalid Zalata, Enas Ezzeldein Fahmy, Sara Missaglia
Article
Clinical Neurology
Alessandro Miola, Nicolo Trevisan, Margherita Salvucci, Matteo Minerva, Silvia Valeggia, Renzo Manara, Fabio Sambataro
Summary: Facial emotion recognition, especially for sadness, is impaired in bipolar disorder. The association between this impairment and brain structure, clinical variables, and subtypes of bipolar disorder remains unclear.
EUROPEAN ARCHIVES OF PSYCHIATRY AND CLINICAL NEUROSCIENCE
(2023)
Review
Clinical Neurology
Mahan Shafie, Elnaz Shahmohamadi, Giulia Cattarinussi, Hossein Sanjari Moghaddam, Shahin Akhondzadeh, Fabio Sambataro, Chiara Moltrasio, Giuseppe Delvecchio
Summary: This review summarizes the findings of resting-state functional magnetic resonance imaging (rsfMRI) studies in individuals with borderline personality disorder (BPD). The results indicate aberrant functional connectivity within and between several brain networks, including the default mode network (DMN), salience network (SN), and central executive network (CEN), as well as selective functional impairments in specific brain regions. However, the generalizability of these results is limited by the observational design, small sample size, and heterogeneity across imaging methodologies.
JOURNAL OF AFFECTIVE DISORDERS
(2023)
Meeting Abstract
Psychiatry
N. Trevisan, F. Di Camillo, G. Cattarinussi, N. Ghiotto, M. Sala, F. Sambataro
EUROPEAN PSYCHIATRY
(2023)
Review
Biochemistry & Molecular Biology
Michele Fornaro, Claudio Caiazza, Niccolo Solini, Michele De Prisco, Martina Billeci, Martina Vannini, Risa Shorr, Stefano Caiolo, Marialaura Lussignoli, Dan Siskind, Giorgio Pigato, Annarita Barone, Fabio Sambataro, Andrea de Bartolomeis, Christoph U. Correll, Marco Solmi
Summary: This study conducted a network meta-analysis on antipsychotic-induced sialorrhea. The results showed that dopamine receptor antagonists, metoclopramide, and sulpiride were effective in treating sialorrhea, while antihistamines and atropine showed no significant effect on nocturnal sialorrhea. This study provides some guidance for the treatment of antipsychotic-related sialorrhea.
MOLECULAR PSYCHIATRY
(2023)
